Al Awwad Specific Aims Doc[1]

Specific Aims: Melanoma, the malignant tumor of melanocytes, occurs mainly in skin and rarely in bowel and eye. The incidence of melanoma is more that 150,000 new cases with mortality rate about 50,000 every year world wide. Melanoma has been therapeutically targeted by very smart alternative agents known as peptides which has a lot of advantages compared with other methods such as monoclonal antibodies. Many combinatorial libraries have been used to find specific ligands for tumor cells. This method is called “one-bead one-compound” which is used for targeting cancer. Our long range goal is to work on development of targeted therapeutics and imaging agents for human and canine melanoma. The objective of this application is to characterize and optimize the melanoma targeting ligands that have been identified in Dr. Lam’s laboratory. The central hypothesis is that cell surface-binding peptide is the best method for targeting cancer. Ligands that bind melanoma cells will be useful for targeting and treatment of melanoma. The central hypothesis will be tested and the objective of this application accomplished by pursuing the following three specific aims: 1) Evaluate the individual targeting potential of the top three ligands using optical imaging methods. 2) Evaluate the pharmacokinetic and therapeutic efficacy of ligand-doxorubicin conjugates in nude mice using human and canine melanoma xerographs model. 3) To select the best ligand in aim 1 and 2, radiolabel it with 99mTc, and to evaluate its biodistribution and tumor uptake in companion dogs with spontaneous melanoma. This work is unique since it works with both human and canine melanoma to identify specific ligands. Hopefully, this study will reveal the pharmacokinetics and therapeutic efficacy of these ligands. We expect the results of this work will be critical since it would give good solutions for melanoma patients.